The anthracycline antibiotic adriamycin is recognized as being among the most valuable of all anticancer agents. Its range of clinical effectiveness includes acute leukemias, lymphomas, and carcinomas of the breast, lung, and thyroid. However, the clinical utility of this drug is hampered by its tendency to produce severe and sometimes fatal cardiotoxicity. Several investigators have linked the development of cardiotoxicity to the presence in the molecule of a quinoid ring system which is capable of supporting the formation of free radicals (e.f., superoxide and hydroxyl) which produce peroxidation of cellular lipids. The heart appears to be particularly vulnerable to this effect since it contains lower levels of protective enzymes (superoxide dismutase, glutathione peroxidase, and catalase) than other tissues. The objective is to develop a better understanding of the relationship between free radical generation and the biological effects produced by quinone-type drugs. Specifically, propose a multi-step synthesis of derivatives of adriamycin which contain an amino group in the chromophore. The electron-donating property of this functionality is expected to lower free radical formation. This should result in a molecule possessing antitumor activity while having a greatly reduced tendency to cause cardiac damage. Several of the steps in the synthesis of the target aglycone have been accomplished on a small scale although some of the low yield steps require improvement. Each of the remaining steps in the scheme has adequate precedent in the literature of anthracycline syntheses. The target aglycone will be converted to a series of glycosides which will be studied using three different pharmacological criteria (superoxide generation, lipid peroxidation, and cardiac response to histamine) in order to assess their cardiotoxic potential. All of the compounds prepared in this study will be subjected to cytotoxicity screening.